Nephrogenic systemic fibrosis (NSF) is a rare and a debilitating disease noted uncommonly in patients with impaired renal function when exposed to low-stability gadolinium-based contrast agents (Gd-CAs). According to experimental studies, cytokines released by the stimulation of effector cells such as skin macrophages and peripheral blood monocytes activate circulating fibroblasts which play a major role in the development of NSF lesions. The presence of permissive factors, presumably, provides an environment conducive to facilitate the process of fibrosis. Multiple treatment modalities have been tried with variable success rates. More research is necessary to elucidate the underlying pathophysiological mechanisms which could potentially target the initial steps of fibrosis in these patients. This paper attempts to collate the inferences from the in vivo and in vitro experiments to the clinical observations to understand the pathogenesis of NSF. Schematic representations of receptor-mediated molecular pathways of activation of macrophages and fibroblasts by gadolinium and the final pathway to fibrosis are incorporated in the discussion.

IntroductionMetastatic bone disease (MBD) carries significant morbidity for patients with cancer. MBD from malignant melanoma (MM) is understudied. We examined the characteristics, morbidity, management and outcome of MBD in patients with MM.MethodsPatients with metastatic MM managed at two referral cancer centres in England were identified. Those with bone metastases (BMs) were selected. Patient and disease characteristics including skeletal related events (SREs) were extracted from medical records. The Kaplan Meier method was used to calculate median survival.ResultsFive hundred and eighteen patients with metastatic MM were managed between years 2000 and 2008. Eighty nine (17.2%) patients had BMs and are the subject of this study. Median age at diagnosis was 53 years and 55% were males. BMs were identified at the time of diagnosis of metastatic disease in 68.5% patients. Sixty-six (74.2%) had multiple bone lesions and 80.9% had axial skeleton involvement. One hundred and twenty nine skeletal related events occurred in 59 (66.3%) patients (50 radiotherapy, 28 hypercalcaemia, 20 bone fractures, 18 spinal cord compression and 13 orthopaedic surgery). The annual skeletal morbidity rate was 2.5.Median survival from diagnosis of BMs was 17.3 weeks and was 5.6 weeks from the first episode of hypercalcaemia.ConclusionMBD affects a clinically important proportion (17.2%) of patients with metastatic MM. It carries a substantial morbidity and mortality exceeding that caused by BMs from breast and prostate cancer. These patients should receive the currently licensed bone modifying agents and should be included in clinical trials addressing MBD.

Nephrogenic systemic fibrosis is a debilitating disorder seen in chronic kidney disease patients and is characterized by stiffening of the joints and thickening of the skin. Treatment options are limited, but some patients have had an improvement of their clinical symptoms after renal transplantation and the use of immunosuppression. Although there is a variable response to renal transplantation, it is currently unknown what factors promote a favorable outcome. Our objective was to evaluate if the response to renal transplantation was superior to other treatment modalities and to determine which characteristics allowed for a positive response to occur. We retrieved the data from the literature of 298 reported patients, compared the response to renal transplantation and to other treatments, and analyzed their characteristics. We found that more patients had a higher response to renal transplantation, as determined by softening of the skin and improved joint mobility, and among those that did respond, they had a shorter dialysis vintage. We suggest that if renal transplantation is to be considered as a treatment modality, it should be initiated at the earliest possible in the course of the disease to achieve maximum clinical benefit.

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